Key Features
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Topical anesthesia is usually sufficient.
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Sterile technique is used.
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Small-gauge needles (30-gauge or smaller) can be used for intravitreal injections.
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Effective method to deliver antivascular endothelial growth factor medications, corticosteroids, antibacterial and antiviral agents, air, and gas.
Associated Features
Complications include:
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Infectious endophthalmitis.
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Sterile inflammation.
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Retinal tears.
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Vitreous hemorrhage.
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Cataract.
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Intraocular pressure elevation; intraocular pressure should be monitored when injecting larger volumes of medication and in patients with glaucoma.
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Different techniques of insertion for multiple platforms of sustained-release implants.
Introduction
The office delivery of medication directly into the vitreous cavity via injection or implant has become commonplace in ophthalmology. This method allows for higher concentrations of medication in the eye with less systemic absorption compared with other methods of administration. In 1911, the injection of air into the vitreous cavity for retinal detachment (RD) repair was initially reported, followed by reports of the injection of penicillin for endophthalmitis in 1947. Fomivirsen (Vitravene; Isis Pharmaceuticals) was the first medication approved by the U.S. Food and Drug Administration (FDA) for intravitreal use in 1998 for the treatment of cytomegalovirus (CMV) retinitis. Pegaptanib (Macugen; OSI Pharmaceuticals), ranibizumab (Lucentis; Genentech), and aflibercept (Eylea; Regeneron Pharmaceuticals) have all since been FDA approved for use in exudative age-related macular degeneration (AMD), and bevacizumab (Avastin; Genentech) is commonly used off-label to treat many forms of choroidal neovascularization and macular edema. The introduction of these vascular endothelial growth factor (VEGF) inhibitors for the treatment of common ocular conditions, such as diabetic retinopathy and exudative AMD, has resulted in a critical need for the ophthalmologist to fully understand the process of performing intravitreal injections.
Preinjection Preparation
Patients for whom intravitreal injection is recommended should be evaluated prior to injection for any signs of ocular infection ( Box 6.13.1 ). Overt, active blepharitis should be treated before injection to decrease the bacterial load, which may increase the risk of infection. Patients with bacterial or viral conjunctivitis should be treated appropriately to manage infection and should have their injection rescheduled. Prophylactic preinjection antibiotics have not been shown to decrease the conjunctival bacterial load compared with application of 5% povidone-iodine prior to injection. There is also concern that routine use of prophylactic antibiotics will increase resistant strains of bacteria on the conjunctival surface without decreasing rates of endophthalmitis. As with any surgical procedure, all patients should sign an informed consent form after being explained the risks, benefits, and alternatives to injection.
Preinjection
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External ocular examination, visual acuity, and intraocular pressure check
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Informed consent form
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Anesthesia (topical or subconjunctival)
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Topical povidone–iodine (5% for the ocular surface, 10% for the lids and lashes)
Injection
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Surgical pause confirming the correct patient, laterality, and medication
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Surgical gloves (sterile or nonsterile)
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Placement of sterile lid speculum or manual lid retraction
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Caliper to measure 3.5–4.0 mm posterior to limbus in preferred quadrant
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5% povidone–iodine to injection site
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Penetration with small gauge needle through conjunctiva and sclera (perpendicular to surface or “tunneled”)
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Slow, steady injection of medication
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Sterile cotton tip applicator at injection site to prevent reflux as needle is removed
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Removal of speculum (if used)
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Maintain sterility of instrument surfaces that contact the eye, prior to injection
Postinjection
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Irrigation of ocular and periocular surfaces with balanced salt solution
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Confirmation of central retinal artery perfusion (visual acuity or direct visualization)
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Intraocular pressure (IOP) check with administration of IOP-lowering medication, if indicated
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Lubricating drops or ointment at end of procedure
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Instruction sheet with information on injection procedure as well as emergency contact number
Pupillary Dilation
Evaluation of central retinal artery perfusion following an intravitreal injection may be required in patients with a history of elevated intraocular pressure (IOP). This may also be beneficial in patients who are receiving larger doses of medication or multiple medications. Dilation may not be required in patients presenting only for injection and who have stable visual acuity and unchanged visual symptoms.
Anesthesia
Topical, subconjunctival, and peribulbar routes of local anesthesia have all been employed for intravitreal injections with similar levels of pain control. Use of topical 0.5% proparacaine or 0.5% tetracaine drops provide adequate analgesia with minimal side effects. A cotton pledget soaked with 4% lidocaine can also be applied to the conjunctival surface. Injection of subconjunctival 2% lidocaine is effective as well but may be associated with subconjunctival hemorrhage, which could be of cosmetic concern to the patient. Topical lidocaine gel is another alternative, but theoretical concerns that the gel may prevent the bactericidal effect of the povidone-iodine have been raised. These are several available options, and different patients may respond more favorably to different forms of anesthesia.
The majority of patients receive their injections in the clinic, with very low complication rates and appropriate analgesia. Furthermore, patients being treated for endophthalmitis may have different anesthesia requirements because of their significant inflammatory response.
Antisepsis
Povidone–iodine is recommended for preinjection antisepsis and has been shown to decrease the rate of endophthalmitis in cataract surgery. It is bactericidal and has rapid cytotoxicity. The periocular lids and lashes can be cleaned with 10% povidone–iodine. Cleaning should begin at the lashes and move peripherally so as not to introduce bacteria to the ocular surface. Gentle cleaning of the lid margin is recommended to prevent discharge of bacteria from the meibomian glands onto the ocular surface, which may otherwise result from vigorous cleaning. The ocular surface is treated with 5% povidone–iodine, which reduces ocular irritation but still has a bactericidal effect. There have been no reported cases of anaphylaxis to povidone–iodine related to ophthalmic use. One may consider referral for skin testing by an allergy specialist for patients reporting any allergies. Allergic contact dermatitis and surface irritation are side effects of povidone–iodine that may result in postinjection discomfort. An endophthalmitis rate of 9.4% has been associated with the failure to use povidone–iodine for injections in patients with self-reported allergies. Chlorhexidine is effective at reducing surgical site infections, and the aqueous form can be used to prepare the ocular surface.
Use of a sterile lid speculum or manual lid retraction is recommended to prevent contact between the tip of the needle and the patient’s lids or lashes. However, this may compress the meibomian glands, resulting in discharge of their contents onto the ocular surface, so an additional application of 5% povidone–iodine may be given prior to injection. The use of gloves (sterile or nonsterile) is considered essential; however, the use of drapes or gowns is not.
Minimal talking or the use of masks after the preparation of the ocular surface is encouraged to prevent airborne contamination by Streptococcus. There is theoretical concern that airborne droplets may settle on the exposed needle prior to injection. Maintaining silence may be difficult, however, in cases where patients require further instruction after sterile preparation.
Pupillary Dilation
Evaluation of central retinal artery perfusion following an intravitreal injection may be required in patients with a history of elevated intraocular pressure (IOP). This may also be beneficial in patients who are receiving larger doses of medication or multiple medications. Dilation may not be required in patients presenting only for injection and who have stable visual acuity and unchanged visual symptoms.
Anesthesia
Topical, subconjunctival, and peribulbar routes of local anesthesia have all been employed for intravitreal injections with similar levels of pain control. Use of topical 0.5% proparacaine or 0.5% tetracaine drops provide adequate analgesia with minimal side effects. A cotton pledget soaked with 4% lidocaine can also be applied to the conjunctival surface. Injection of subconjunctival 2% lidocaine is effective as well but may be associated with subconjunctival hemorrhage, which could be of cosmetic concern to the patient. Topical lidocaine gel is another alternative, but theoretical concerns that the gel may prevent the bactericidal effect of the povidone-iodine have been raised. These are several available options, and different patients may respond more favorably to different forms of anesthesia.
The majority of patients receive their injections in the clinic, with very low complication rates and appropriate analgesia. Furthermore, patients being treated for endophthalmitis may have different anesthesia requirements because of their significant inflammatory response.
Antisepsis
Povidone–iodine is recommended for preinjection antisepsis and has been shown to decrease the rate of endophthalmitis in cataract surgery. It is bactericidal and has rapid cytotoxicity. The periocular lids and lashes can be cleaned with 10% povidone–iodine. Cleaning should begin at the lashes and move peripherally so as not to introduce bacteria to the ocular surface. Gentle cleaning of the lid margin is recommended to prevent discharge of bacteria from the meibomian glands onto the ocular surface, which may otherwise result from vigorous cleaning. The ocular surface is treated with 5% povidone–iodine, which reduces ocular irritation but still has a bactericidal effect. There have been no reported cases of anaphylaxis to povidone–iodine related to ophthalmic use. One may consider referral for skin testing by an allergy specialist for patients reporting any allergies. Allergic contact dermatitis and surface irritation are side effects of povidone–iodine that may result in postinjection discomfort. An endophthalmitis rate of 9.4% has been associated with the failure to use povidone–iodine for injections in patients with self-reported allergies. Chlorhexidine is effective at reducing surgical site infections, and the aqueous form can be used to prepare the ocular surface.
Use of a sterile lid speculum or manual lid retraction is recommended to prevent contact between the tip of the needle and the patient’s lids or lashes. However, this may compress the meibomian glands, resulting in discharge of their contents onto the ocular surface, so an additional application of 5% povidone–iodine may be given prior to injection. The use of gloves (sterile or nonsterile) is considered essential; however, the use of drapes or gowns is not.
Minimal talking or the use of masks after the preparation of the ocular surface is encouraged to prevent airborne contamination by Streptococcus. There is theoretical concern that airborne droplets may settle on the exposed needle prior to injection. Maintaining silence may be difficult, however, in cases where patients require further instruction after sterile preparation.
Injection
The needle used for injection need be no larger than 30-gauge for a routine injection of medication or gas. Use of a smaller-gauge needle may reduce procedural discomfort in patients. The force required to penetrate the sclera is almost doubled when using a 27-gauge needle compared with a 30- or 31-gauge needle. Needle length should be 5/8 of an inch or shorter to prevent globe trauma. The majority of retinal specialists surveyed in 2010 reported using a 30-gauge needle for injections of bevacizumab and ranibizumab, and a 27-gauge needle for triamcinolone. Triamcinolone can precipitate within the syringe and clog a needle smaller than 30-gauge. Separate needles should be used to remove the medication from the vial (usually a filter needle) and to perform the actual injection (30–32 gauge). This helps prevent both contamination and dulling of the needle.
The injection is given through the pars plana approximately 3.5–4.0 mm posterior to the limbus. Injections are commonly performed in the inferotemporal and superotemporal quadrants. The quadrant of injection may be influenced by the indication for injection or other factors. For example, injecting an opaque corticosteroid superiorly may initially obscure the visual axis more compared with an inferiorly administered injection. Similarly, a patient with a large inferotemporal retinoschisis cavity may benefit from having the injection given in another quadrant.
The traditional injection method involves inserting the needle perpendicular to the sclera in a single plane to penetrate the globe, although tunneling methods have also been described. The final needle direction should always be toward the center of the eye to prevent damage to other intraocular contents.
The medication should be injected in a slow, steady manner to prevent a sudden flux through the vitreous cavity because this may disrupt vitreoretinal adhesions. A sterile cotton tip applicator may be used to prevent reflux after needle removal. Injection of larger volumes of medication (e.g., for endophthalmitis) may require removal of aqueous or vitreous humor to prevent IOP elevation.
Postinjection
The use of topical antibiotics following intravitreal injections had previously been a common practice but is no longer recommended. Recent clinical trials have demonstrated that postinjection topical antibiotics may not be required for patients undergoing routine intravitreal injections of anti-VEGF or corticosteroid medications. Routine use of topical fluoroquinolones after injections has been shown to increase rates of antibiotic resistance of conjunctival flora.
The ocular and periocular surfaces should be irrigated to remove the povidone–iodine. Lubricating drops or ointment may be placed on the eye to alleviate ocular discomfort associated with the povidone–iodine preparation.
IOP elevation is common after intravitreal injection but remains below 35 mm Hg in the majority of patients. Patients with glaucoma may be more susceptible to IOP elevation. IOP can be monitored following injection and topical medications given, if needed. Anterior chamber paracentesis should not be performed routinely after each injection to lower IOP. However, injection of larger volumes or multiple medications may require paracentesis. The presence of at least light perception vision suggests that the central retinal artery is perfused, but the most reliable method to confirm perfusion is direct visualization with the indirect ophthalmoscope.
Prior to leaving the office after the injection, the patient should be counseled regarding ocular care at home and about symptoms that would require evaluation prior to the next scheduled visit. Appropriate education regarding expected side effects from the povidone–iodine preparation and intravitreal injection, versus symptoms of injection complications, may help avoid unnecessary concern or additional visits ( Table 6.13.1 ). Providing an instruction sheet in large print with the above information, as well as a 24-hour contact number, is beneficial.
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